University of California, Los Angeles, Los Angeles, California.
Montreal Neurological Institute, Montreal, Quebec, Canada.
JAMA Oncol. 2020 Dec 1;6(12):1939-1946. doi: 10.1001/jamaoncol.2020.3161.
New treatments are needed to improve the prognosis of patients with recurrent high-grade glioma.
To compare overall survival for patients receiving tumor resection followed by vocimagene amiretrorepvec (Toca 511) with flucytosine (Toca FC) vs standard of care (SOC).
DESIGN, SETTING, AND PARTICIPANTS: A randomized, open-label phase 2/3 trial (TOCA 5) in 58 centers in the US, Canada, Israel, and South Korea, comparing posttumor resection treatment with Toca 511 followed by Toca FC vs a defined single choice of approved (SOC) therapies was conducted from November 30, 2015, to December 20, 2019. Patients received tumor resection for first or second recurrence of glioblastoma or anaplastic astrocytoma.
Patients were randomized 1:1 to receive Toca 511/FC (n = 201) or SOC control (n = 202). For the Toca 511/FC group, patients received Toca 511 injected into the resection cavity wall at the time of surgery, followed by cycles of oral Toca FC 6 weeks after surgery. For the SOC control group, patients received investigators' choice of single therapy: lomustine, temozolomide, or bevacizumab.
The primary outcome was overall survival (OS) in time from randomization date to death due to any cause. Secondary outcomes reported in this study included safety, durable response rate (DRR), duration of DRR, durable clinical benefit rate, OS and DRR by IDH1 variant status, and 12-month OS.
All 403 randomized patients (median [SD] age: 56 [11.46] years; 62.5% [252] men) were included in the efficacy analysis, and 400 patients were included in the safety analysis (3 patients on the SOC group did not receive resection). Final analysis included 271 deaths (141 deaths in the Toca 511/FC group and 130 deaths in the SOC control group). The median follow-up was 22.8 months. The median OS was 11.10 months for the Toca 511/FC group and 12.22 months for the control group (hazard ratio, 1.06; 95% CI 0.83, 1.35; P = .62). The secondary end points did not demonstrate statistically significant differences. The rates of adverse events were similar in the Toca 511/FC group and the SOC control group.
Among patients who underwent tumor resection for first or second recurrence of glioblastoma or anaplastic astrocytoma, administration of Toca 511 and Toca FC, compared with SOC, did not improve overall survival or other efficacy end points.
ClinicalTrials.gov Identifier: NCT02414165.
需要新的治疗方法来改善复发性高级别神经胶质瘤患者的预后。
比较接受肿瘤切除后接受 vocimagene amiretrorepvec（Toca 511）联合氟胞嘧啶（Toca FC）与标准治疗（SOC）的患者的总生存期。
设计、地点和参与者：这是一项在美国、加拿大、以色列和韩国的 58 个中心进行的随机、开放标签的 2/3 期试验（TOCA 5），比较了肿瘤切除后接受 Toca 511 联合 Toca FC 治疗与 SOC 单一批准治疗方案的疗效。试验从 2015 年 11 月 30 日至 2019 年 12 月 20 日进行，患者接受了胶质母细胞瘤或间变性星形细胞瘤的首次或第二次复发的肿瘤切除术。
患者被随机分为 1:1 接受 Toca 511/FC（n=201）或 SOC 对照组（n=202）。对于 Toca 511/FC 组，患者在手术时将 Toca 511 注入切除腔壁，然后在手术后 6 周接受口服 Toca FC 治疗。对于 SOC 对照组，患者接受研究者选择的单一治疗：洛莫司汀、替莫唑胺或贝伐珠单抗。
主要终点是从随机分组日期到任何原因导致的死亡的总生存期（OS）。本研究报告的次要终点包括安全性、持久缓解率（DRR）、DRR 持续时间、持久临床获益率、OS 和按 IDH1 变异状态的 DRR 以及 12 个月 OS。
所有 403 名随机患者（中位数[SD]年龄：56[11.46]岁；62.5%[252]为男性）均纳入疗效分析，400 名患者纳入安全性分析（SOC 组的 3 名患者未接受切除术）。最终分析包括 271 例死亡（Toca 511/FC 组 141 例，SOC 对照组 130 例）。中位随访时间为 22.8 个月。Toca 511/FC 组的中位 OS 为 11.10 个月，SOC 对照组为 12.22 个月（风险比，1.06；95%CI，0.83，1.35；P=0.62）。次要终点未显示出统计学意义上的差异。Toca 511/FC 组和 SOC 对照组的不良事件发生率相似。
在接受肿瘤切除术治疗胶质母细胞瘤或间变性星形细胞瘤首次或第二次复发的患者中，与 SOC 相比，Toca 511 和 Toca FC 的给药并未改善总生存期或其他疗效终点。
ClinicalTrials.gov 标识符：NCT02414165。
